Aconitine-induced cardiac arrhythmia in human induced pluripotent stem cell-derived cardiomyocytes.

Pre-clinical evaluation of cardiac dysfunction is important for assessing the safety of traditional or novel medicines due to the universality of potential drug-induced heart failure and irreversible arrhythmia. Aconitine (ACO), a traditionally used anti-pyretic, analgesic and anti-rheumatic drug, has been reported to have arrhythmogenic effects. In the present study, the Real-Time Cellular Analysis Cardio system was applied to evaluate the arrhythmogenic effects of ACO in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The results indicated that ACO is capable of increasing the frequency and decreasing the amplitude of hiPSC-CM contraction in a dose- and time-dependent manner. ACO at 0.25 µM increased the beating rate of hiPSC-CMs by 3.7-fold within 30 min, while 3.0 µM of ACO increased the beating rate by 7.3-fold. The present study also evaluated the potential pro-apoptotic effects of ACO by using caspase-3 and caspase-9 kits. To the best of our knowledge, the present study was the first to record the ACO-induced cardiac arrhythmia of hiPSC-CMsin real-time. The results also indicate that ACO-induced cell death is mediated, at least in part, by caspase-dependent apoptotic pathways.